Octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study run to international guideline but not GLP, but published in a peer reviewed journal.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 428 (Skin Absorption: In Vitro Method)

Deviations:

not specified

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine

EC Number:

220-260-0

EC Name:

Octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine

Cas Number:

2691-41-0

Molecular formula:

C4H8N8O8

IUPAC Name:

1,3,5,7-tetranitro-1,3,5,7-tetrazocane

Test material form:

solid: crystalline

Details on test material:

- Name of test material (as cited in study report): HMX
- Substance type: explosive
- Physical state: crystalline powder
- Radiochemical purity (if radiolabelling): 97.7%
- Specific activity (if radiolabelling): 6.84 mCi/mmol
- Locations of the label (if radiolabelling): ring- 14C

Radiolabelling:

yes

Test animals

Species:

pig

Strain:

other: Yorkshire

Sex:

female

Administration / exposure

Type of coverage:

open

Vehicle:

acetone

Duration of exposure:

24 h

Doses:

10 μg/cm2

Details on in vitro test system (if applicable):

SKIN PREPARATION
- Source of skin: female Yorkshire pigs
- Type of skin: whole skin from upper back of pig
- Preparative technique: dermatomed
- Thickness of skin (in mm): 0.5-0.9 mm
- Membrane integrity check: no but under same conditions, pigskin shown to maintain viability for at least 50h (Reifenrath and Hawkins, 1986)
- Storage conditions: 12 h at 4°C

PRINCIPLES OF ASSAY
- Diffusion cell: stainless-steel version of the low volume flow cell (Reifenrath et al, 1994)
- Receptor fluid: RPMI tissue culture medium
- Solubility of test substance in receptor fluid: unknown
- Static system: yes
- Flow-through system: no
- Test temperature: unknown
- Humidity: unknown
- Occlusion: no
- Reference substance(s): no


- Reifenrath, W. G., Lee, B., Wilson, D. R., and Spencer, T. S. (1994). A comparison of in vitro skin-penetration cells. J. Pharm. Sci. 83, 1229–1233.
- Reifenrath, W. G., and Hawkins, G. S. (1986). The weanling Yorkshire pig as an animal model for measuring percutaneous penetration. In Swine in
Biomedical Research, 1st ed. (M. E. Tumbleson, Ed.), pp. 673–680. Plenum, New York.

Results and discussion

Signs and symptoms of toxicity:

not specified

Dermal irritation:

not specified

Absorption in different matrices:

- Receptor fluid : 0.1 ± 0.1% of applied radioactive dose
- Epidermis : 16 ± 4% of applied radioactive dose
- Dermis : 3 ± 2% of applied radioactive dose
- Stratum corneum : 73 ± 8% of applied radioactive dose
- Evaporation : 0.09 ± 0.02% of applied radioactive dose

Total recovery:

- Total recovery: 97 ± 3% of applied radioactive dose

Percutaneous absorption

Dose:

10 μg/cm2

Parameter:

percentage

Absorption:

4 %

Remarks on result:

other: 24 h

Applicant's summary and conclusion

Conclusions:

The percentage of absorption of HMX in acetone in an in vitro pig skin absorption method was 4%